Grants

2020-07-15 to 2024-06-30 | Grant
National Heart Lung and Blood Institute (Bethesda, US)
URL: https://app.dimensions.ai/details/grant/grant.9329558
GRANT_NUMBER: R01HL147866
Organization identifiers
FUNDREF: http://dx.doi.org/10.13039/100000050
National Heart, Lung, and Blood Institute: Md., Md., US
Total funding amount
USD 2,874,773
Description
Abstract Current clinical criteria for treatment of atherosclerotic plaque, or atheromas, have focused primarily on percent stenosis of the vessel. However, measures of occlusion (percent stenosis) do not identify those plaques that are prone to rupture, which may release emboli into the blood stream feeding sensitive cerebral vasculature. A novel approach, Lagrangian carotid strain imaging, where tissue displacements are precisely measured during pulsation of blood through the artery has been developed. We propose to measure `strain indices,’ that include the maximum accumulated axial, lateral, and shear strain estimated over the cardiac cycle, to probe the detailed mechanical properties of early plaque. We believe these strain indices will prove to be valuable vascular biomarkers to indicate vascular aging and possible plaque vulnerability. Our preliminary results demonstrate the ability to differentiate between soft and stiff regions in plaque under in-vivo clinical imaging conditions. Our definition of `vulnerable plaque’ or `vulnerable patient’ relies on the identification of lipidic depositions or softer plaques, i.e., those that undergo large axial or lateral deformations and/or large shearing strains during the cardiac cycle. Capability of strain tensor imaging and vascular biomarkers to characterize plaque severity from its early stages to a mature plaque lesion will be evaluated and quantified. A study on asymptomatic volunteers and patients also is proposed. The volunteer will provide values for vascular strain indices normalized to age-related vascular stiffening. The results will enable us to establish trends in age-related variations in vascular stiffness and to determine deviations that could establish vascular aging criteria. Interventions to reverse vascular aging might then be used, for example lifestyle modifications and common medical therapies. Strain imaging results will be validated and complimented by three- dimensional (3D) carotid magnetic resonance imaging (MRI) on a selected group of high-risk volunteers, along with 3D carotid MRI and 3D histopathological analysis of the entire excised plaque on patients to better understand plaque composition and structure. Validation of our results will foster use of real-time noninvasive ultrasound strain imaging as a screening tool for identifying human subjects susceptible to vascular aging and/or developing plaque prone to rupture or micro-embolization that could lead to `silent strokes’ and possible vascular cognitive impairment. The patient study will also enable comparison of strain indices and carotid MRI to the ground truth, namely the excised plaque.

2015-03-06 to 2016-03-05 | Grant
NIH Office of the Director (Bethesda, US)
URL: https://grants.uberresearch.com/100000052/S10OD018505/Ultrasonic-and-Photoacoustic-Imaging-System-for-Cancer-Cardiovascular-Research
GRANT_NUMBER: S10OD018505
Organization identifiers
RINGGOLD: 35053
National Institutes of Health Office of the Director: Bethesda, MD, US
Other organization identifiers provided by RINGGOLD
ISNI: 0000000405338641
OFR: http://dx.doi.org/10.13039/100000052
Total funding amount
USD 907,915
Description:The goal of this shared instrumentation proposal is to develop effective small animal imaging capabilities in the Wisconsin Institutes for Medical Research (WIMR), specifically to implement innovative preclinical ultrasound and photoacoustic imaging capabilities. We are respectfully requesting funds to purchase the Visualsonics Vevo(R) LAZR Photoacoustic Imaging system, with transducers and supporting equipment that will enable superficial and deep imaging of tumors and other disease models, physiological monitoring, and effective high speed recording of perfusion, strain, and molecular tagging agents. This high-resolution, micro imaging system was devised specifically for non-invasive small animal research. It can deliver in vivo visualization of structures at the embryonic level through the adult mouse in real time and has the ability to perform longitudinal studies of disease progression and regression. With resolution of anatomical and physiological structures down to 30 microns and the ability to visualize image-guided needle injection and extraction, microcirculatory and cardiovascular blood flow assessments, the system has applications in many different disciplines that use the mouse, rat or other small animals for its model system. WIMR based investigators of 13 major projects and 8 minor projects describe the integration of the array-based ultrasound and photoacoustic system into their research. The Vevo(R) LAZR not only bolsters existing studies, but also provides exciting and important new information, combining quantitative imaging with advanced biological assessments to monitor progression/regression of disease and effectiveness of therapeutics. Comprehensive educational and marketing plans will inform researchers throughout the UW medical school and campus on ways that the system could enhance their own research. A business model that includes modest user fees and a strong institutional commitment from the Medical Physics department, the Carbone Cancer Center, and the School of Medicine and Public Health assures the system will continue to benefit researchers for the lifetime of the instrument.

2009-09-30 to 2012-08-31 | Grant
National Institute of Biomedical Imaging and Bioengineering (Bethesda, US)
URL: https://grants.uberresearch.com/100000002/R21EB010098/Vulnerable-Plaque-Detection-with-Carotid-Strain-Imaging
GRANT_NUMBER: R21EB010098
Total funding amount
USD 406,519
Description: Current clinical criteria for treatment of atherosclerotic plaque or atheromas, has focused primarily on percent stenosis of the vessel. However, percent stenosis does not identify plaque prone to rupture that may release emboli into the blood stream of the sensitive cerebral vasculature. These ‘vulnerable’ plaques are particularly prone to produce sudden major problems, such as a heart attack or stroke. Atheromas become vulnerable if they grow rapidly and have only a thin fibrous cap separating the soft lipid pool and other plaque constituents from the bloodstream. Structural stability of carotid plaque is a result of its chemical composition, cellular material and new vessel formation. Various studies have indicated that pulsatile pressure induced due to blood flow may rupture the thin cap overlying lipid rich lesions, leading to subsequent thrombosis and plaque rupture. Plaque vulnerability is therefore determined primarily by the mechanical (elastic) properties of the vessel wall and plaque composition. Ultrasound-based strain imaging can provide a means of identifying vulnerable plaque. A novel approach to strain imaging, where pulsation of blood through the carotid artery is used to induce tissue displacements for strain imaging, will be developed and evaluated. We propose the use of three ‘strain indices’ namely; maximum accumulated axial strain, maximum lateral displacement and strain, and shear strains in plaque over the cardiac cycle as measures of plaque vulnerability. To obtain the normal and shear strain tensors, we propose to utilize beam-steered radiofrequency data acquired along different angular insonification directions to compute the displacement vectors and subsequently the strain tensors. We will also incorporate a modified dynamic 2D multi-level cross-correlation method to track local displacements with the angular data acquired. Our preliminary results demonstrate the ability to differentiate between soft and stiffer plaque noninvasively. The long term objectives are to provide a non-invasive measurement of patients at risk for plaque rupture, expanding upon the current criteria for treatment for atherosclerotic risk based on focal transient ischemic attacks or strokes. The limited in-vivo study on patients will be complimented by a similar analysis on a control group of age-matched volunteers to determine the significance of the ‘strain indices’ for discrimination of vulnerable plaque. Finally, the entire excised plaque core following carotid endarterectomy will be further evaluated using histological analysis at the same in-vivo transverse cross-sections (based on measurements from the flow- divider) where strain imaging was performed to better understand plaque composition and structure (along with microulcerations and neovascularity) to the information displayed on the normal and shear strain images.

2009-07-01 to 2012-06-30 | Grant
National Cancer Institute (Bethesda, US)
URL: https://grants.uberresearch.com/100000054/R21CA140939/Uterine-In-vivo-Strain-Imaging-Using-Saline-Infusion
GRANT_NUMBER: R21CA140939
Total funding amount
USD 359,370
Description: The overall goal of this research is to develop technology for imaging uterine masses and identifying diffuse pathological conditions using ultrasound strain imaging or elastography. Postmenopausal bleeding is a common gynecological problem, accounting for nearly 5% of office visits. Though the majority of cases result from a benign etiology (endometrial atrophy or hyperplasia, polyps, leiomyomas), approximately 10% to 30% of women will be found to have endometrial cancer. One of the features of cancer is the relative rigidity of the surrounding neoplastic tissue. We hypothesize that elastography could usefully be applied to the diagnosis of postmenopausal bleeding by distinguishing diffuse stiff endometrial tissue (cancer), diffuse endometrial soft tissue (hyperplasia), focal stiff masses (leiomyomas), and focal soft masses (polyps). Differentiation between fibroids and adenomyosis in the uterus is another area where stiffness variation may provide a means of diagnosis. Uterine fibroids and adenomyosis have a similar appearance on conventional US scans, making differentiation problematic- if not impossible- for the sonologist. This differentiation is, however, clinically important because treatment for the two conditions is very different, and clinicians must now use more expensive but less accessible imaging tests. Our research will develop ultrasound strain imaging for differentiating between these two conditions. Three specific aims are proposed in the R21 phase of this research. The first investigates the stiffness contrast that is present between normal and abnormal uterine tissue. Young’s modulus measurements will be done on excised uterine samples obtained following hysterectomy procedures. Secondly, strategies for optimizing the timing between mechanical deformation and data acquisition in the uterus for in vivo saline induced sonohysterography (SIS) based strain imaging will be studied using anthropomorphic phantoms. Phantoms will also be utilized to optimize displacement tracking and strain estimation performance with the multi-level algorithm proposed for sector strain imaging. Thirdly, the research will also investigate the feasibility of utilizing SIS based strain imaging in-vivo. This will be done by applying the method to 15-20 human patients and evaluating uterine mass delineation/ differentiation and the ability to identify diffuse uterine pathology. Exvivo strain images will be obtained of intact uterine specimens when they become available for comparisons with these in-vivo imaging results. Preliminary in-vivo results presented in the proposal (Fig. 10 and 11) strongly indicate that our approaches will be effective. Thus, this feasibility project will likely lead to future in depth clinical trials.

2006-05-01 to 2010-04-30 | Grant
Susan G. Komen Breast Cancer Foundation (Dallas, US)
URL: https://app.dimensions.ai/details/grant/grant.100074898
GRANT_NUMBER: BCTR0601153
Organization identifiers
FUNDREF: http://dx.doi.org/10.13039/100000869
Susan G. Komen for the Cure: TX, TX, US
Total funding amount
USD 249,990
Description: Breast cancer remains the second-leading cause of cancer deaths in women, and over 200,000 new cases of invasive breast cancer are expected in the United States this year alone. As suggested by The American Cancer Society, breast self examination and clinical breast examination (palpation) are the most frequently used diagnostic tools for detecting breast abnormalities. In our research, we propose to utilize a new imaging technique termed elastography, to determine the elastic properties of tissue. The practice of elastography can be considered to be a ‘high-tech’ form of palpation, Imaging of tissue elastic parameters for diagnosis and treatment is rapidly gaining attention because of the ability to provide noninvasive and new diagnostic information. In elastography, we typically estimate the axial strain (along the direction of insonification/compression) by analyzing ultrasonic signals obtained from standard medical ultrasound diagnostic equipment. elastography has been used for imaging and characterizing tumors in breast, and other biological tissue. Since ultrasonic visualization is widely used in practically all-medical specialties. The proposed technique could therefore have a large impact on medical practice in the United States . We have developed a new technique of producing shear strain images in elastography using angular ultrasound data. Shear strain elastograms enable the differentiation of infiltrating carcinomas from benign fibroadenomas. Since cancers infiltrate into surrounding normal tissue and include calcifications and spiculations, they may be far less mobile and not slip during compression as do fibroadenomas. Shear strain elastograms estimated from the normal strain tensors derived here have the potential for clearly depicting sliding or slippage of such masses that may occur during compression thereby differentiating fibroadenomas from cancers.

2004-12-01 to 2018-04-30 | Grant
National Cancer Institute (Bethesda, US)
URL: https://grants.uberresearch.com/100000054/R01CA112192/Real-time-Ultrasonic-Monitoring-of-Tumor-Ablation
GRANT_NUMBER: R01CA112192
Total funding amount
USD 2,588,816
Description: Minimally invasive treatments are essential for patients with liver tumors that do not respond to chemotherapy and for patients with inoperable liver cancers. Radiofrequency (RF) and microwave (MW) ablation techniques are interstitial, focal therapies that are being used with increasing frequency for these cases. Image guidance for placement of RF or MW probes and for initial assessments of treated volumes is essential for the success of these procedures. We and others have demonstrated that ultrasound based strain and modulus imaging are promising for accurately depicting the treated volumes in ablation procedures. Initial assessments for superficial structures demonstrate high image contrast of ablated regions. Our research will develop and evaluate a novel strain imaging method termed electrode displacement elastography, or EDE, to monitor minimally invasive ablative treatments and delineate the zone of necrosis regardless of the depth of treatment. We will initially test the effectiveness of EDE using echo data acquired with conventional curvilinear and phased arrays. This will be done by imaging custom tissue-mimicking phantoms with Young’s Modulus values equivalent to that of liver tissue to determine reliability of mapping out ablated and partially ablated regions for various EDE acquisition parameters. Finite element analysis (FEA) to model deformations induced by RF/microwave displacements will be performed to better understand these experimental results. We then will evaluate 2D EDE on human patients, acquiring data at typical imaging depths and for various liver states, i.e. cirrhotic liver for hepatocellular carcinoma (HCC) and softer livers with stiffer tumors for metastases. Comparisons between EDE strain and follow-up X-ray CT images will provide crucial information on the effectiveness of EDE strain images to delineate the zone of necrosis. We will then develop and test bi-plane and three-dimensional (3D) volumetric EDE strain and modulus imaging using a 2D matrix phased array transducer. Accuracy of ablation boundary delineation for different echo data acquisition conditions will be determined using tissue-mimicking phantoms. In-vivo studies will then be conducted to test bi-plane and 3D EDE for strain and modulus imaging both on a wood-chuck HCC model and a rabbit VX2 metastases model to evaluate depiction and delineation of cancers before and after ablation therapy. Comparisons of the strain and modulus images with histopathology using light microscopy of ablated tissue will be performed. Finally, a pilot study will be performed using percutaneous bi-plane and 3D EDE on human patients. Successful completion of these studies will pave the way for clinical trials using EDE for monitoring minimally invasive ablative therapies. Incidence of HCC has doubled in the last decade, with a mortality rate of 3-6 months without treatment. The clinical significance of accurate ultrasound-based guidance for ablation treatments will be high, both in terms of reducing patient morbidity and of lowering treatment costs.

2004-08-16 to 2007-07-31 | Grant
National Institute of Biomedical Imaging and Bioengineering (Bethesda, US)
URL: https://grants.uberresearch.com/100000002/R21EB003853/Normal-Shear-Strain-Imaging-From-Angled-US-Acquisition
GRANT_NUMBER: R21EB003853
Total funding amount
USD 530,207
Description: The current practice of elastography, images only the axial component of the strain tensor, while the lateral and elevational strain tensor components are basically disregarded. In the absence of lateral and elevational components, other important elastic parameters such as shear strains and Poisson’s are not imaged. Moreover, efforts at reconstruction of the Young’s modulus from strain data would be significantly improved if all the normal and shear strain tensors are available. In this research, we propose a novel method of estimating displacements and strains in axial, lateral and elevational directions in ultrasound elastography imaging. The method uses tissue displacement components estimated along multiple angular ultrasound beam directions acquired with linear array transducers. Strain elastograms of normal and shear tensors are then calculated from the axial and lateral displacement information in addition to Poisson’s ratio information. The research plan develops and optimizes this method for a state-of-the-art scanner using simulations to evaluate tradeoffs between acquisition rate, angles and data accuracy. Implementation of the techniques will be on the Siemens Antares scanner, capitalizing on a newly developed ultrasound research interface to facilitate angular beam data acquisition and control. Tests using elastography phantoms will yield performance benchmarks. Two new phantom types will also be developed to evaluate the ability to derive the fundamental information expected in these images. Finally, excised tissue samples will be imaged to evaluate the new elasticity information obtained. Clinical applications where the methodology will be directed are in differentiating malignant from benign masses in the breast and thyroid. In both sites lateral slippage is believed to occur in many benign masses when the tissue is compressed, while slippage appears to be absent with malignant masses. The proposed lateral and shear strain images are expected to be particularly sensitive to such phenomena.

2023-04-01 to 2026-03-31 | Grant
PI: Randall Kimple, MD
National Institute of Dental and Craniofacial Research (Bethesda, US)
URL: https://app.dimensions.ai/details/grant/grant.13305295
GRANT_NUMBER: UH3DE030431
Organization identifiers
FUNDREF: http://dx.doi.org/10.13039/100000072
National Institute of Dental and Craniofacial Research: Md., Md., US
Funding subtype
Funding sub-type
Total funding amount
USD 604,753

2021-07-01 to 2023-03-31 | Grant
PI: Randall Kimple, MD
National Institute of Dental and Craniofacial Research (Bethesda, US)
URL: https://app.dimensions.ai/details/grant/grant.9734808
GRANT_NUMBER: UG3DE030431
Organization identifiers
FUNDREF: http://dx.doi.org/10.13039/100000072
National Institute of Dental and Craniofacial Research: Md., Md., US
Total funding amount
USD 311,832
Description: Dry mouth is a significant side-effect of radiation therapy for head and neck cancer patients. Several factors contribute to dry mouth. Decreased production of saliva is called hyposalivation. Poor quality and function of saliva is called salivary dysfunction. Together, these cause xerostomia, or what a patient experiences as simply dry mouth. Xerostomia can lead to tooth decay, infections, difficulty speaking, impaired swallowing, poor nutrition, and has a significant negative effect on quality of life. Doctors recommend that patients suck on hard candy, chew gum, use saliva substitutes, and/or carry a water bottle with them at all times. None of these are particularly effective. Our long-term goal is to improve outcomes for patients suffering from radiation-induced dry mouth. We seek to achieve this goal by providing convincing evidence that innovative cellular therapies can safely and significantly improve salivary gland function and quality of life. The team of investigators tackling this project is uniquely suited to complete the work. Success would lead directly to the next phase of clinical testing. We have expertise in caring for head and neck cancer patients, developing bone marrow derived mesenchymal stromal cells (MSCs) as cellular therapies, and studying salivary function. The overall objective of this application is to perform a Phase 1 trial to test the safety and tolerability of IFN-g pre-licensed MSCs for treatment of radiation-induced xerostomia in head and neck cancer patients. To achieve our goals, we propose two aims spread across the two phases of this application. In Aim 1, we will work closely with the NIH, NIDCR, and FDA to complete all necessary milestones to activate the proposed clinical trial (Aim 1) and enroll our first patient (UG3 phase). In Aim 2, we will perform a Phase 1 safety and tolerability study of IFN-g pre-licensed autologous MSCs in patients with radiation-induced xerostomia in order to define the recommended phase 2 dose (UH3 phase). An expansion cohort at the recommended phase 2 dose (n=12 additional patients) will be included in order to confirm the safety profile, better describe the toxicity, and investigate the efficacy of MSC injection to treat radiation-induced xerostomia. We will assess the efficacy using both validated patient-reported outcome measures and through assessment of salivary production and composition. This trial is expected to provide key data used to design the next clinical trial. A phase 2 study would further test the efficacy of MSCs in head and neck cancer patients. These studies will also provide important data to support future grant applications aimed at improving the salivary response through ex vivo engineering of MSCs.

2010-03-15 to 2017-01-31 | Grant
PI: Robert J. Dempsey, MD
National Institute of Neurological Disorders and Stroke (Bethesda, US)
URL: https://app.dimensions.ai/details/grant/grant.2562387
GRANT_NUMBER: R01NS064034
Organization identifiers
FUNDREF: http://dx.doi.org/10.13039/100000065
National Institute of Neurological Disorders and Stroke: Md., Md., US
Total funding amount
USD 1,536,211
Description
Description: This study examines the issue of “silent” strokes in the relationship between the structural stability of atherosclerotic carotid plaque and the development of nonmotor symptomatology, including brain atrophy and cognitive decline. It addresses the question of the role of carotid emboli in “silent” stroke and their cognitive sequelae. The study uses human carotid endarterectomy patients to study three specific aims. The first uses ultrasound to relate plaque elasticity and its development of mechanical strain features with pulsation and the histopathophysiology of the plaque for ulcer, hemorrhage and thinning of stabilizing fibrous cap at the point of these mechanical strain features. The second examines ultrasound detected elasticity strain features in the plaques and the presence of transcranial Doppler TCD detectable microemboli. The third looks at ultrasound strain deficits, microemboli, cognitive decline and brain MRI evidence of focal and generalized atrophy. Understanding the structural plaque abnormalities, which render a carotid plaque mechanically unstable and at risk of embolization will demonstrate a pathophysiologic mechanism in individuals who are likely to suffer not only classic episodic major strokes, but also functional progressive decline from the contribution of microemboli to cerebral “silent” stroke and cognitive decline.

2004-04-01 to 2010-02-28 | Grant
PI: Timothy J Hall, Ph.D
National Cancer Institute (Bethesda, US)
URL: https://app.dimensions.ai/details/grant/grant.2476656
GRANT_NUMBER: R01CA100373
Organization identifiers
FUNDREF: http://dx.doi.org/10.13039/100000054
National Cancer Institute: Md., Md., US
Total funding amount
USD 1,556,494
Description: Breast cancer is the second-leading cause of cancer deaths in women. Over 200,000 new cases of invasive breast cancer are expected in the USA this year alone. It is anticipated that nearly 40,000 women in the USA would die of breast cancer in 2002. Breast self examination and clinical breast examination (palpation) are the most frequently used diagnostic tools for detecting breast abnormalities, and most breast abnormalities are detected with palpation. The overall goal of this project is the development of tools that will improve the classification of breast lesions, particularly in mammographically-dense breasts using elasticity imaging. The basis of the proposed work is our successful real-time implementation of elasticity imaging on a commercially available ultrasound scanner and initial in vivo results on patients with breast disease. Measurements of the bulk elastic properties of in vitro tissues showed that most breast tissues have non-linear stress-strain relationships, but the non-linearity was highest in cancers. We have observed relative non-linearity in mechanical strain among in vivo breast tissue in our preliminary studies. To enhance and extend that work, we propose the following specific aims: 1) significantly improve the quality of strain image sequences through improved motion tracking and error detection and correction; 2) improve the data acquisition and computational capacity and flexibility of the clinical system by porting the application to a new platform (the Siemens Antares); 3) interface a pressure sensor array to the clinical sonography system to provide data acquisition feedback and encode and display the nonlinearity in the stress-strain relationship of tissues; 4) test these methods with simulated data and experiments with phantoms and human subjects; 5) develop tools to teach clinicians the standard measurement techniques for estimating bulk material properties, such as Young’s modulus, how to adapt those techniques to scanning the human body. The result of this effort will be a clinically useful tool for examining the mechanical response of human tissues, and a set of training tools to allow the skilled ultrasound clinician to efficiently learn to use these new tools.

2003-09-19 to 2006-08-31 | Grant
PI: James A Zagzebski, Ph.D
National Institute of Biomedical Imaging and Bioengineering (Bethesda, US)
URL: https://app.dimensions.ai/details/grant/grant.2610038
GRANT_NUMBER: R21EB002722
Organization identifiers
FUNDREF: http://dx.doi.org/10.13039/100000070
National Institute of Biomedical Imaging and Bioengineering: Md., Md., US
Total funding amount
USD 425,849
Description: In gray scale imaging, the most widely used clinical ultrasound modality, only the amplitudes of ultrasound echo signals are detected and displayed as dots on the monitor. However, the emergence of a new class of computer-controlled ultrasound scanning machines represents an outstanding opportunity to implement novel parametric imaging modes that should significantly compliment conventional scanning paradigms. Our goals are to implement and test scatterer size, integrated backscatter and attenuation imaging modes on a clinical scanner. The scanner is also being equipped with various elastography imaging, which will enable these data also to be included. Parametric images will be constructed by applying data reduction techniques that incorporate echo data from a reference phantom to account for imaging system and transducer dependencies of echo data. Scatterer size images will be constructed by applying least squares data reduction routines to fit spectral data to a model, where a free parameter represents the scatterer size. Integrated backscatter is considered the best representation of the scattered energy from a region, where corrections for attenuation and system dependencies on echo data are applied. New attenuation images and region of interest attenuation calculations will be incorporated that also apply reference phantom methods. Means for prerecording reference phantom information into the scanner memory will be evaluated, which would provide absolute internally calibrated ultrasound image data. Although images of scatterer size, integrated backscatter, and tissue strain have been previously reported, they have been plagued by the presence of noise artifacts especially for image data that are generated using echo signal spectra. We propose to improve the SNR of parametric images by spatially compounding parametric images obtained using RF data acquired at different insonification angles of the ultrasound beam. Angular compounding of the parametric images allows multiple, independent estimations of spectral parameters from each image voxel. In addition, angular compounding provides a means of improving images of axial tissue strain (elastograms) obtained by weighted angular compounding. The work is primarily directed towards ultrasound breast tissue imaging, where a research scanner being acquired by the Departments of Medical Physics and Radiology is being sited. Preliminary data will be generated for this application.